Microdialysis monitoring of liver grafts by metabolic parameters, cytokine production, and complement activation.
BACKGROUND
The outcome of liver transplantation is steadily improving. Still there is need for earlier detection of complications like hepatic artery thrombosis and rejection. The aim of this study was to explore whether microdialysis with a 100-kDa cutoff filter could be used to monitor local inflammation after liver transplantation.


METHODS
Twenty patients undergoing liver transplantations were observed for 1 week posttransplant. Microdialysis catheters were introduced in each liver lobe subcutaneously and metabolic parameters (glucose, pyruvate, glycerol, and lactate), cytokines (interleukin [IL]-6, IL-8, monocyte chemottractic protein-1, and inducible protein [IP]-10), and complement activation (C5a) were measured.


RESULTS
Fourteen patients experienced an uneventful course, judged clinically by ultrasound Doppler and by metabolic markers including lactate and the ischemia indicator lactate-to-pyruvate ratio. All patients with uneventful course had a consistent rise in IP-10 from 200 to 3000 pg/mL after transplantation, whereas the other cytokines stayed low. Two patients with rejection showed a selective increase in IL-8 and C5a, starting 2 to 4 days before alanine transferase increased, reaching 10- to 50-fold increase compared with baseline levels, and decreased rapidly after start of antirejection therapy. C5a concentration was substantially increased in these two patients at the time of transplantation. A third patient developed a hepatic artery thrombosis and rejection and showed a rapid rise in intrahepatic lactate and a complex inflammatory pattern.


CONCLUSIONS
Microdialysis using a 100-kDa filter is a promising way of monitoring the inflammatory reaction after liver transplantation. Increase in IP-10 reflects a normal pathophysiologic response posttransplant, whereas IL-8 and C5a were increased only in patients with rejection.
Waelgaard
Lars
L
Department of Anaesthesia and Critical Care Medicine, Rikshospitalet, University Hospital, University of Oslo, Oslo, Norway.
Thorgersen
Ebbe Billmann
EB
Line
Pål-Dag
PD
Foss
Aksel
A
Mollnes
Tom Eirik
TE
Tønnessen
Tor Inge
TI
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation; D015936:Complement C5a / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D006505:Hepatitis / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008567:Membranes, Artificial; D017551:Microdialysis / Q000295:instrumentation; D008875:Middle Aged; D008970:Molecular Weight; D008991:Monitoring, Physiologic / Q000295:instrumentation / Q000379:methods*; D013927:Thrombosis / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8; D008567:Membranes, Artificial; D015936:Complement C5a